Li Yaoming, Xu Min, Chen Long, Zhu Jinghui, Ye Jing, Liu Xueqin, Sun Yanfang, Chen Huanchun, Cao Shengbo
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, PR China.
Vaccine. 2009 Oct 9;27(43):6004-10. doi: 10.1016/j.vaccine.2009.07.078. Epub 2009 Aug 7.
Japanese encephalitis (JE) is a serious infectious disease in southern and eastern Asia. Design and development of safer and more efficacious vaccines against Japanese encephalitis virus (JEV) is a high-priority target in the world. Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) playing a central and unique role in the generation of primary T-cell responses, and are considered attractive "live adjuvants" for vaccination and immunotherapy against cancer and infectious diseases. In this study, mouse bone marrow-derived dendritic cells (bmDCs were generated and stimulated with inactivated JEV in vitro. BALB/c mice were immunized with stimulated bmDCs and then challenged with JEV wild-type strain. The neutralization antibody, interferon gamma (IFN-gamma), tumor necrosis factors alpha (TNF-alpha) or interleukin-6 (IL-6), and virus-specific CD8+ cytotoxic T-lymphocyte (CTL) levels, as well as survival rates, were analyzed and compared with inactivated vaccine and DCs control groups. The results demonstrated that intravenous (i.v.) injection of 2 x 10(5) JEV-pulsed bmDCs into each mouse produced notable levels of JEV-specific neutralizing antibodies and higher levels of CD8+ CTL, IFN-gamma and TNF-alpha compared with JEV-inactivated vaccine. Furthermore, stimulated bmDCs could elicit a highly protective efficacy (90%) against JEV challenge. It suggests that stimulated bmDCs can be considered as an attractive "live adjuvant" for vaccination against JEV infection.
日本脑炎(JE)是南亚和东亚地区的一种严重传染病。设计和开发更安全、更有效的抗日本脑炎病毒(JEV)疫苗是全球的一个高度优先目标。树突状细胞(DCs)是最强大的专职抗原呈递细胞(APCs),在初始T细胞反应的产生中发挥着核心且独特的作用,并且被认为是用于癌症和传染病疫苗接种及免疫治疗的有吸引力的“活佐剂”。在本研究中,从小鼠骨髓中生成树突状细胞(bmDCs),并在体外用灭活的JEV进行刺激。用刺激后的bmDCs对BALB/c小鼠进行免疫,然后用JEV野生型毒株进行攻击。分析并比较了中和抗体、干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)或白细胞介素-6(IL-6)以及病毒特异性CD8+细胞毒性T淋巴细胞(CTL)水平,还有存活率,与灭活疫苗组和DCs对照组进行比较。结果表明,与JEV灭活疫苗相比,每只小鼠静脉注射(i.v.)2×10⁵个JEV脉冲的bmDCs可产生显著水平的JEV特异性中和抗体以及更高水平的CD8+ CTL、IFN-γ和TNF-α。此外,刺激后的bmDCs可引发针对JEV攻击的高度保护效力(90%)。这表明刺激后的bmDCs可被视为用于预防JEV感染疫苗接种的有吸引力的“活佐剂”。